Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide and accounts for 500,000 deaths each year (Okuda 2000). The survival rate of HCC patients has not been improved over the past 20 years, with the incidence rate almost equal to the death rate (Marrero, Fontena et al. 2005). The known major risk factors for HCC are chronic hepatitis resulting from infection with hepatitis B virus or hepatitis C virus and exposure to carcinogens such as aflatoxin B1 (Thorgeireson and Grisham 2002).
It was reported that the change in cell cycle regulators that proceed to the GI phase in the cell cycle leads to hepatocarcinogenesis [Hui et al., Hepatogasteroenterology 45:1635-1642, 1998]. In addition, it was reported that DNA mutations and genetic alterations in gene expression are found in the tissue of liver cancer patients [Park et al., Cancer Res. 59:307-310, 1999; Bjersing et al., J. Intern. Med. 234:339-340, 1993; Tsopanomichalou et al., Liver 19:305-311, 1999; Kusano et al., Hepatology 29:1858-1862, 1999; Keck et al., Cancer Genet. Cytogenet. 111:37-44, 1999].
Thus, it can be seen that the development and progression of cancer is not caused by some specific genes, but results from complex interactions between many genes that are involved in various intracellular signaling mechanisms and regulatory mechanisms which occur during the progression of cancer. Accordingly, it is very significant to identify new liver cancer-related genes by comparatively analyzing the expression levels of a large number of genes between normal liver cells and liver cancer cells, rather than studying mechanisms of hepatocarcinogenesis on the basis of some specific genes.
Recent molecular studies revealed that genetic alterations of tumor suppressor genes or oncogenes, such as p53, beta-catenin and AXIN1, can be associated with the progression of HCC (de La Coste, Romagnolo et al. 1998; Satoh, Daigo et al. 2000; Pang, Ng et al. 2003). However, it is unclear whether such genetic alterations are reflected in the clinical characteristics of tumors of individuals. Thus, reliable molecular studies on HCC in most patients still remain challenges (Nam, Park et al. 2005).
Accordingly, the present inventors have analyzed the expression level of the SIRT7 gene in cancer tissues, and as a result, have identified a cancer diagnostic marker that expresses SIRT7, as well as specific miRNAs that function to regulate the expression of SIRT7. The present inventors have also found that the miRNAs have the abilities to regulate the cell cycle and inhibit tumor growth caused by promoter methylation, and thus can be used as a cancer therapeutic target, thereby completing the present invention.